title: Tbc1d15-17 regulates synaptic development at the Drosophila neuromuscular junction.
abstract: Members of the Tre-2/Bub2/Cdc16 (TBC) family of proteins are believed to function as GTPase-activating proteins (GAPs) for Rab GTPases, which play pivotal roles in intracellular membrane trafficking. Although membrane trafficking is fundamental to neuronal morphogenesis and function, the roles of TBC-family Rab GAPs have been poorly characterized in the nervous system. In this paper, we provide genetic evidence that Tbc1d15-17, the Drosophila homolog of mammalian Rab7-GAP TBC1d15, is required for normal presynaptic growth and postsynaptic organization at the neuromuscular junction (NMJ). A loss-of-function mutation in Tbc1d15-17 or its presynaptic knockdown leads to an increase in synaptic bouton number and NMJ length. Tbc1d15-17 mutants are also defective in the distribution of the postsynaptic scaffold Discs-large (Dlg) and in the level of the postsynaptic glutamate subunit GluRIIA. These postsynaptic phenotypes are recapitulated by postsynaptic knockdown of Tbc1d15-17. We also show that presynaptic overexpression of a constitutively active Rab7 mutant in a wild-type background causes a synaptic overgrowth phenotype resembling that of Tbc1d15-17 mutants, while a dominant-negative form of Rab7 has the opposite effect. Together, our findings establish a novel role for Tbc1d15-17 and its potential substrate Rab7 in regulating synaptic development.
authors.affiliation: Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Sooyeon
authors.initials: S
authors.lastname: Jang
authors.forename: Minyeop
authors.initials: M
authors.lastname: Nahm
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Yoon
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; C586989:Tbc1d15-17 protein, Drosophila; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins